Nebulization of Endotoxin during Mechanical Ventilation

An Experimental Model of ARDS in Pigs
  • J. C. Pompe
  • J. Kesecioğlu
  • H. A. Bruining
  • C. Ince
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 388)


Gram-negative sepsis is the most common setting in the ICU in which abnormalities in lung function known as the Adult Respiratory distress Syndrome (ARDS) develops1. Lipo-polysaccharide molecules residing in the outer membrane of gram-negative bacteria (endotoxins), are the bacterial components presumed to elicit the inflammatory response of the host that underlie the etiology of ARDS. ARDS is associated with significant abnormalities of lung mechanics2,3. Decreased compliance with resultant rapid shallow breathing and increased deadspace ventilation, not refractory hypoxemia, are often rate-limiting factors preventing weaning from mechanical ventilation in patients with esthablished ARDS4. Decreases in compliance are also associated with increased airway pressure in the mechanically ventilated patient and with the development of macroscopic barotrauma5. The pathophysiology of lung injury induced by endotoxin has been studied extensively in vivo after intravenous or intraperitoneal infusion of endotoxin in a wide variety of animal models, using different methods and species, including the rat6, pig7, dog8 and sheep9. However, responses to intravenous infusion nearly always include symptoms of systemic involvement, with varying degrees of hemodynamic instability as a result. The same problem exist in other models of ARDS such as lung-lavage and oleic acid infusion. In order to produce a stable model in these instances, aggressive volume and inotropic support is usually necessary. As a result, treatment strategies under investigation are difficult to evaluate.


Mean Arterial Pressure Adult Respiratory Distress Syndrome Pancuronium Bromide Peak Airway Pressure Refractory Hypoxemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Newman JH. Sepsis and pulmonary edema. Clin Chest Med 1985; 6:371–91.PubMedGoogle Scholar
  2. 2.
    Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967;2:319–323.PubMedCrossRefGoogle Scholar
  3. 3.
    Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988; 138:720–723.PubMedGoogle Scholar
  4. 4.
    Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. New Engl J Med 1991; 324:1445–1450.PubMedCrossRefGoogle Scholar
  5. 5.
    Hinson JR, Marini JJ. Principles of mechanical ventilator use in respiratory failure. Annu Rev Med 1992; 43:341–361.PubMedCrossRefGoogle Scholar
  6. 6.
    Rinaldo JR, Dauber MH, Christman J, Rogers RM. Neutrophil alveolitis following endotoxemia: enhancement by previous exposure to hyperoxia. Am Rev Respir Dis 1984; 130:1065–1071.PubMedGoogle Scholar
  7. 7.
    Steinberg SM, Dehring DJ, Gower JR, Vento JM, Lowery FF, Cloutier CT. Prostacyclin in experimental septic acute respiratory failure. J Surg Res 1983; 34:298–302.PubMedCrossRefGoogle Scholar
  8. 8.
    Krausz MM, Utsunomiya T, Feuerstein G, Wolfe JHN, Shepiro C, Hechtman HP. Prostacyclin reversal of lethal endotoxemia in dogs. J Clin Invest 1981; 67:1118–1125.PubMedCrossRefGoogle Scholar
  9. 9.
    Ebenshade AM, Newman J, Lams P, Jolles H, Brigham K. Respiratory failure after endotoxin infusion in sheep: lung mechanics and fluid balance. J Appl Physiol 1979; 53:967–976.Google Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • J. C. Pompe
    • 1
  • J. Kesecioğlu
    • 2
  • H. A. Bruining
    • 1
  • C. Ince
    • 3
  1. 1.Departments of SurgeryUniversity Hospital RotterdamThe Netherlands
  2. 2.Department of AnesthesiologyUniversity Hospital RotterdamThe Netherlands
  3. 3.Department of AnesthesiologyAcademic Medical Center University of AmsterdamThe Netherlands

Personalised recommendations